Contrast media (or contrast agents) and their use in the diagnostic filed are widely described in literature.
In particular, iodinated aromatic derivatives are among the classes of compounds that find an application as contrast agents in diagnostic techniques which relying on the absorption of X rays by the tissues or organs (i.e. radiography, tomography). Among these aromatic iodinated derivatives it is worth mention, inter alia, Iohexol (GB 1,548,594—Nyegaard & Co. A/S) Ioversol (EP 83964—Mallinckrodt Inc.), Iopamidol (GB 1,472,050—Bracco) and Iomeprol (EP 365541—Bracco). These iodinated contrast agents are prepared by various synthetic routes described in literature, whereby some of such synthetic route comprise the poly-iodination of an aromatic intermediate, in particular a phenol or aniline derivative intermediate, by means of different iodinating agents. More specifically, EP773923 (Bracco) describes the iodination of 5-amino-1,3-benzenedicarboxylic acid with iodine chloride (ICl) in the presence of hydrochloric acid, to give the corresponding tri-iodine derivative according to the following scheme:

A substantially similar approach was also described for the iodination of 5-hydroxy-1,3-benzenedicarboxylic acid as reported, for example, in EP 782562 (Bracco). ICl can be prepared by methods known to the expert in the field, some of which contemplate the formation of a chlorinated species of I (III), typically ICl3, and the subsequent conversion of the thus obtained intermediate, by the addition of molecular I2, as schematically set forth below:

Among the possible methods to generate ICl3 it may be mentioned, for instance, the use of KClO3 by reaction with I2 in the presence of hydrochloric acid (Acta Chim. Slovo. 2000, 47, 89-90) or the preparation according to JP 1141803 (Mitsui Toatsu Chemicals) that requires the use of gaseous chlorine as initial reagent:

Although this latter route enables the production of ICl with a high degree of purity, the use of gaseous chlorine, especially in an application on an industrial scale, involves the need of strict precautions and safety arrangements because of the toxicity and hazard of that gas.
Advantageously, we have now found a process for the preparation of ICl in high yields and high purity, which does not require the use of gaseous chlorine, avoiding thereby the above mentioned drawbacks typically associated with the use of large volumes of chlorine.